TY - JOUR T1 - SARS-CoV-2 Spike S1 Receptor Binding Domain undergoes Conformational Change upon Interaction with Low Molecular Weight Heparins JF - bioRxiv DO - 10.1101/2020.04.29.068486 SP - 2020.04.29.068486 AU - Courtney J. Mycroft-West AU - Dunhao Su AU - Yong Li AU - Scott E. Guimond AU - Timothy R. Rudd AU - Stefano Elli AU - Gavin Miller AU - Quentin M. Nunes AU - Patricia Procter AU - Antonella Bisio AU - Nicholas R. Forsyth AU - Jeremy E. Turnbull AU - Marco Guerrini AU - David G. Fernig AU - Edwin A. Yates AU - Marcelo A. Lima AU - Mark A. Skidmore Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/29/2020.04.29.068486.abstract N2 - The dependence of the host on the interaction of hundreds of extracellular proteins with the cell surface glycosaminoglycan heparan sulphate (HS) for the regulation of homeostasis is exploited by many microbial pathogens as a means of adherence and invasion. The closely related polysaccharide heparin, the widely used anticoagulant drug, which is structurally similar to HS and is a common experimental proxy, can be expected to mimic the properties of HS. Heparin prevents infection by a range of viruses when added exogenously, including S-associated coronavirus strain HSR1 and inhibits cellular invasion by SARS-CoV-2. We have previously demonstrated that unfractionated heparin binds to the Spike (S1) protein receptor binding domain, induces a conformational change and have reported the structural features of heparin on which this interaction depends. Furthermore, we have demonstrated that enoxaparin, a low molecular weight clinical anticoagulant, also binds the S1 RBD protein and induces conformational change. Here we expand upon these studies, to a wide range of low molecular weight heparins and demonstrate that they induce a variety of conformational changes in the SARS-CoV-2 RBD. These findings may have further implications for the rapid development of a first-line therapeutic by repurposing low molecular weight heparins, as well as for next-generation, tailor-made, GAG-based antiviral agents, against SARS-CoV-2 and other members of the Coronaviridae.Competing Interest StatementThe authors have declared no competing interest. ER -